Symptoms and General Pathology

All Conditions

Nervous System Diseases

Recurrence

Pain

Breakthrough Pain

Neurologic Manifestations

Adjuvants, Anesthesia

Analgesics

Central Nervous System Depressants

All Drugs and Chemicals

Fentanyl

Morphine

Analgesics, Opioid

Narcotics

Anesthetics

Anesthetics, Intravenous

Anesthetics, General

Hospitalized participants asked to complete a number of surveys at baseline. Participants then receive one single dose of intravenous opioid rescue for their first episode of breakthrough pain, and then receive up to 4 doses of FSS for subsequent episodes of breakthrough pain. Initial FSS starting dose is proportional to the patient's morphine equivalent daily dose (MEDD). Symptom questionnaire completed at baseline and after last dose of FSS while hospitalized. Mental ability tests given while hospitalized 30 minutes after first dose of current pain medication, and 30 minutes after each FSS dose. At the time of discharge, if FSS was helpful in controlling participant's pain, they are then able to continue with FSS use for 1 month. Participants given study diary to document pain level, how many times FSS used, and any side effects experienced each day.

Stage 1: First Pain Episode - Single dose of breakthrough opioid given from existing PCA pump equivalent to 10% of their MEDD.

Second Pain Episode - Single dose of FSS equivalent to 16-32% of MEDD. If not effective at 30 minutes, participant repeats same dose one more time (with a cap of 1600 mcg total; i.e. dose given 30 minutes ago + dose now = 1600 mcg maximum.

Third Pain Episode (at least 4 hours after second episode) - Participant required 2 breakthrough FSS doses for the last episode of breakthrough pain, or if the effective dose has not been identified, he/she will double the last administered dose. If breakthrough pain not effective at 30 minutes, participant repeats same dose one more time (with a cap of 1600 mcg total; i.e. dose given 30 minutes ago + dose now = 1600 mcg maximum).

Stage 2: If FSS successful in hospital, upon discharge, FSS used as first choice of pain medication instead of oral pain medication for pain for up to 4 weeks.

Fentanyl Sublingual Spray (FSS)

Symptom questionnaire completed at baseline and after last dose of FSS while hospitalized. After Day 28, questionnaire completed over the phone about participant's opinion of research study.

Questionnaires

Mental ability tests given while hospitalized 30 minutes after first dose of current pain medication, and 30 minutes after each FSS dose.

Mental Ability Tests

Participants given study diary to document pain level, how many times FSS used, and any side effects experienced each day.

Study Diary

Suresh Reddy, MD

The goal of this clinical research study is to learn if an investigational dose of fentanyl sublingual spray (FSS) can help to control pain in patients with advanced cancer when given in an outpatient and inpatient setting.

Study Visits and Study Drug Administration:

This study has 2 stages. Stage 1 will be completed while you are in the inpatient unit of the hospital and Stage 2 will be completed after you are discharged from the hospital.

Stage 1:

While you are in the hospital, if you have a pain episode, the research nurse will give you a single dose of your current pain medication from your existing infusion pump. You will then be asked to rate your current level of pain . You will also be asked if you are having any side effects at 15 minutes and at 30 minutes after the dose has been administered. You will also complete the 4 tests of mental abilities after about 30 minutes.

If after 1-4 hours you have another episode of pain, you will be given a single dose of FSS. You will spray FSS under your tongue and hold it there for about 30-60 seconds before swallowing. You will be asked about your current level of pain at about 15 minutes and 30 minutes after your dose of FSS. You will also complete the 4 tests of mental abilities after about 30 minutes. If you do not feel any pain relief after 30 minutes, you will spray FSS 1 more time under your tongue and you will repeat the pain and mental ability tests.

If you still do not feel any pain relief after about 4 hours from the last dose of FSS, you will spray a double dose of FSS under your tongue up to 2 times and your pain level and mental abilities will be tested at 15 and 30 minutes after each dose.

You may receive FSS up to 4 times total while you are in the hospital.

After your last dose of FSS, you will complete a questionnaire about how your symptoms are after receiving FSS. This should take about 2 minutes to complete.

End of Stage 1:

If FSS was able to help you control your pain, you will stop taking FSS and go back to receiving your regular pain medication for the rest of your hospital stay. When you are discharged from the hospital, you will continue on to Stage 2 of the study (described below) to receive FSS for up to 4 weeks at home. Before you are sent home, you will also be prescribed pain medication to take in addition to the FSS, if needed. Your doctor will explain how to take this medication before you are discharged.

If FSS was not able to help control your pain, your participation in this study will end and you will continue to be treated with standard pain medications.

Stage 2:

If you are taking part in Stage 2, you will use FSS as your first choice of pain medication instead of oral pain medication for pain for up to 4 weeks. At any time that you have a pain episode, you will spray FSS under your tongue.

You will always have the choice of using the pain medication your doctor prescribed to you as a backup every 2 hours as needed for pain. However, it is very important that you do NOT use the oral pain medications at the same time as FSS. If you still have pain after taking FSS, you must wait at least 2 hours before using your pain medications. After 2 more hours if you have another episode of pain, you may use another dose of FSS for pain relief.

Do not take more than 4 doses of FSS each day.

You will be given a patient diary to write down each day your pain level, how many times you used FSS, and any side effects you may have. You will be called at least 2 times each week by a member of the study staff to discuss your diary and to answer any questions you may have. The study staff will also ask you which pain medication you are using besides FSS, how easy you think it is to use FSS, how effective you think FSS is, and how satisfied you are with your current pain medications. Each phone call should last about 10 minutes.

After Day 28, you will complete a questionnaire over the phone about your opinion of this research study. This should take about 5 minutes to complete.

Length of Study:

Your active participation in this study is over after you complete the last questionnaire. You will be taken off study if intolerable side effects occur or if you are unable to follow study directions.

Follow-Up:

About 30 days after your study visit, you will be called by the study staff and asked how you are feeling and about any side effects you may be having. This call should last about 10 minutes.

This is an investigational study. FSS is FDA approved and commercially available for the treatment of pain in cancer patients. It is considered investigational to use the dose of FSS used in this study and to use FSS both in inpatient and outpatient settings.

About 30 participants will be enrolled in this study. All will take part at MD Anderson.

Sublingual Fentanyl for the Management of Breakthrough Pain

A Preliminary Study of Sublingual Fentanyl for the Management of Breakthrough Pain Analgesia in Patients With Advanced Cancer

To determine the effective dose of Fentanyl sublingual spray in the management of breakthrough pain (4 episodes) in hospitalized patients with advanced cancer receiving continuous opioid infusion in which the first starting dose would be proportional to the patients Morphine Equivalent Daily Dose. It will use Alberta Breakthrough Pain assessment tool with 15 questions.

To estimate the differences in the pain response between intravenous opioid breakthrough and fentanyl sublingual spray at effective dose. Pain will be assessed in a 0-10 numeric rating scale that assesses pain intensity now, where 0=no pain at all, and 10=worst possible.

To determine the safety, tolerability, pattern of use and efficacy of Fentanyl sublingual spray in patients with advanced cancer

INSYS Therapeutics Inc

M.D. Anderson Cancer Center

Fentanyl sublingual spray was administered with a starting dose of 100 mcg up to 1600 mcg maximum for each breakthrough pain.

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Married

Separated/Divorced

Marital status

Some high School

Some College

Completed College

Did not answer

Education

Colon

Gastric

Melanoma

Cholangiocarcinoma

Lymphoma

Cancer Type

Suresh K. Reddy, MD/Professor, Palliative Care Med

Data was not collected due to low accrual and early termination.

Effective Dose of Fentanyl Sublingual Spray (FSS)

Difference Between Intravenous Opioid and Fentanyl Sublingual Spray

Safety, Tolerability, Pattern of Use and Efficacy

Overall Study

Mouth and Tooth Diseases

Digestive System Diseases

Stomatitis

Mucositis

Gastroenteritis

Gastrointestinal Diseases

Mouth Diseases

Stomatognathic Diseases

Participants received a single administration of fentanyl sublingual spray 100 µg sublingually.

Fentanyl was supplied in single-dose glass vials assembled into a delivery device to be used as a sublingual spray.

Fentanyl sublingual spray

Lisa J. Stearns, MD

This was an open-label, single-dose study to assess the safety, tolerability, and absorption/distribution kinetics of a single 100 µg dose of fentanyl sublingual spray in opioid-tolerant cancer subjects, with or without oral mucositis.

RATIONALE: One dose of fentanyl sublingual spray may be effective in relieving pain in opioid-tolerant cancer patients.

PURPOSE: This phase III trial is studying the side effects of fentanyl sublingual spray and to see how well it works in treating opioid-tolerant cancer patients with or without oral mucositis.

OBJECTIVES:

Primary

* To compare the absorption/distribution kinetics of a single dose of fentanyl sublingual spray in opioid-tolerant cancer patients with or without oral mucositis.
* To evaluate the safety and tolerability of this regimen.

OUTLINE: This is a multicenter study.

Patients fast for at least 8 hours before and at least 4 hours after and no water is allowed for at least 1 hour before and at least 1 hour after study drug administration. Patients receive a single dose of fentanyl sublingual spray while in an upright position in clinical care recliners or beds, and remain in an upright posture for at least 4 hours after administration. Patients are instructed not to swallow for at least 5 minutes after administration and not to expectorate the drug.

After study drug administration, 10 blood samples are collected over a 12-hour period for pharmacokinetic and other analyses.

Fentanyl Sublingual Spray in Treating Opioid-tolerant Cancer Patients With or Without Oral Mucositis

Evaluate Safety and Tolerability and Compare Absorption/Distribution Kinetics of a Single 100 Mcg Dose of Fentanyl Sublingual Spray (Fentanyl SL Spray) in Cancer Subjects With or Without Oral Mucositis

Cmax is defined as the maximum drug concentration in plasma and was determined from individual plasma concentration versus time data. Blood samples for pharmacokinetic analysis were drawn pre-dose; 15 and 30 minutes; and 1, 2, 4, 6, 8, 10, and 12 hours post-dose. Fentanyl concentration assays were performed using a fully validated and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Results are reported for patients with and without mucositis.

Tmax is defined as the time to reach the maximum concentration of fentanyl in plasma and was determined from individual concentration versus time data. Blood samples for pharmacokinetic analysis were drawn pre-dose; and 15 and 30 minutes; and 1, 2, 4, 6, 8, 10, and 12 hours post-dose. Fentanyl concentration assays were performed using a fully validated and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Results are reported for patients with and without mucositis.

AUC0-last is defined as the area under the plasma concentration-time curve from time-zero to the time of the last quantifiable concentration of fentanyl, was calculated using the linear trapezoidal rule, and was determined from individual concentration versus time data. Blood samples for pharmacokinetic analysis were drawn pre-dose; and 15 and 30 minutes; and 1, 2, 4, 6, 8, 10, and 12 hours post-dose. Fentanyl concentration assays were performed using a fully validated and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Results are reported for patients with and without mucositis.

Safety population: All subjects who received study drug.

Fentanyl Sublingual Spray 100 µg - Mucositis

Fentanyl Sublingual Spray 100 µg - Non-mucositis

Fentanyl Sublingual Spray 100 µg

Age Continuous

Larry Dillaha, M.D., Chief Medical Officer

Pharmacokinetic (PK) population: All subjects who had evaluable plasma profiles to calculate reliable estimates of PK parameters and who had no major protocol deviations. One subject in the non-mucositis group self-administered a fentanyl product before receiving the study drug and was excluded from the PK population due to this protocol deviation.

Cmax of Fentanyl

Tmax of Fentanyl

Pharmacokinetic evaluable population: All subjects who had evaluable plasma profiles to calculate reliable estimates of pharmacokinetic parameters and who had no major protocol deviations.

AUC0-last of Fentanyl

Respiratory Tract (Lung and Bronchial) Diseases

Dyspnea

Respiration Disorders

Respiratory Tract Diseases

Signs and Symptoms, Respiratory

Questionnaires completed at baseline and at end of study visit. Participant performs Shuttle Walk Test before and after receiving low-dose Fentanyl sublingual spray. Four mental ability tests completed after each walk test. Low-dose Fentanyl sprayed into mouth and under tongue one hour after first Shuttle Walk Test.

Questionnaires completed at baseline and at end of study visit. Participant performs Shuttle Walk Test before and after receiving high-dose Fentanyl sublingual spray. Four mental ability tests completed after each walk test. High-dose Fentanyl sprayed into mouth and under tongue one hour after first Shuttle Walk Test.

Low-dose Fentanyl Goup: 15-25% of the morphine equivalent daily dose (MEDD) sprayed into mouth and under tongue one hour after first Shuttle Walk Test.

High-Dose Fentanyl Group: 35-45% of the morphine equivalent daily dose (MEDD) sprayed into mouth and under tongue one hour after first Shuttle Walk Test.

Fentanyl Sublingual Spray

Participants walk back and forth between 2 cones in an indoor hallway for up to 12 minutes. After one hour Fentanyl Spray delivered, then second walk test performed.

Shuttle Walk Test

Questionnaire completed about any breathing problems or other symptoms participant may be having at baseline. End of study questionnaire asks which dose level of study drug participant thinks they received. Participant also completes a questionnaire about how study drug may have helped them and how satisfied they are with the study. It should take about 5 minutes to complete the questionnaire.

After each walk test, participant completes 4 tests of their mental abilities. It should take 15 minutes total to complete these tests.

Thirty days study visit participant called by study staff. This call should last about 10 minutes.

Phone Call

David Hui, MD

The goal of this clinical research study is to learn if fentanyl can help shortness of breath in cancer patients. Researchers also want to learn if the study drug can help to improve your physical function.

If you agree to take part in this study, the study staff will collect information from your medical record about your age, sex, race, and disease type, as well as how well you are able to perform the normal activities of daily living, any drugs you are taking, and any possible causes of shortness of breath.

Study Groups:

You will be randomly assigned (as in the flip of a coin) to receive either low-dose or high-dose fentanyl spray. This is done because no one knows if one study group is better, the same, or worse than the other group.

Study Visit:

During your study visit, you will complete 2 questionnaires about any breathing problems or other symptoms you may be having. It should take about 10 minutes total to complete these questionnaires.

You will blow into a device called a spirometer a few times to measure your lung function. You will also be asked to inhale into another device called a negative inspiratory force meter (NIF). This device measures the volume of air that can be inhaled after normal breathing.

The study staff will then record your vital signs (heart rate, breathing rate, blood pressure, and your blood-oxygen level). Your blood-oxygen level will be measured with a device that will be clipped gently onto your fingertip). You will then be asked how hard it is to catch your breath and to rate your level of tiredness.

When instructed, you will walk back and forth between 2 cones in an indoor hallway for up to 12 minutes. This is called the Shuttle Walk Test. The purpose of this timed test is to see how far and fast you can walk without stopping for a rest. You will be asked to pivot briskly around the cones and continue back the other way. You may stop this test at any time if you feel you cannot continue.

After that, you will sit down and rest for up to 1 hour. During this time, the study drug will be prepared, and you may be asked at different times how hard it is to catch your breath.

After the rest period, you will be given the fentanyl to spray into your mouth and under your tongue. About 10 minutes later, you will be asked about any side effects you may be having.

At that point, you will perform a second Shuttle Walk Test. Then the study staff will ask you again about any side effects you may be having, your level of tiredness, and how hard it is to catch your breath. Your vital signs will also be measured. The total distance you walked will also be recorded.

After each walk test, you will also be asked to complete 4 tests of your mental abilities, including finger tapping, simple math questions (addition, subtraction, multiplication, division), recall of numbers, and recall of objects. It should take 15 minutes total to complete these tests.

At the end of the study visit, you will be asked which dose level of the study drug you think you received (high-dose or low-dose). You will also complete a questionnaire about how the study drug may have helped you and how satisfied you are with the study. It should take about 5 minutes to complete the questionnaire.

At the end of the study, if you think that taking fentanyl helped to improve your breathing, your doctor will be told, so that you and your doctor may discuss if fentanyl would be helpful to you in the future.

Length of Study:

Your active participation in this study is over after you complete the last questionnaire. You will be taken off study if intolerable side effects occur or if you are unable to follow study directions.

Follow-Up:

Fourteen (14) days after your study visit you will be called by the study staff and asked how you are feeling and about any side effects you may be having. This call should last about 10 minutes.

This is an investigational study. Fentanyl is FDA approved and commercially available for the treatment of pain. Its use to control shortness of breath is investigational.

Up to 30 participants will be enrolled in this study. All will take part at MD Anderson.

Fentanyl Sublingual Spray for Exercise-Induced Breakthrough Dyspnea

A Preliminary Study of Prophylactic Fentanyl Sublingual Spray for Exercise-Induced Breakthrough Dyspnea

The primary outcome was dyspnea intensity "now" using the modified Borg scale, which ranges from 0 ("no shortness of breath") to 10 ("worst possible shortness of breath"). We measured the change in modified dyspnea Borg scale (0-10) between the first and second shuttle walk tests. This scale has been validated in multiple studies, with a minimal clinically significant difference of 1 point.

The modified Borg scale (dyspnea unpleasantness), which ranges from 0 ("no shortness of breath") to 10 ("worst possible shortness of breath"). We measured the change in modified dyspnea Borg scale (0-10) between the first and second shuttle walk tests.

We measured the difference in walk distance (in meters) between the first and second shuttle walk tests.

We measured the difference in walk time (in minutes) between the first and second shuttle walk tests.

The fatigue modified Borg scale, which ranges from 0 ("none") to 10 ("worst"). We measured the change in modified fatigue Borg scale (0-10) between the first and second shuttle walk tests.

Received Fentanyl sublingual spray 10 minutes before performing second shuttle walk test, dose was 35-45% of morphine equivalent daily dose.

Intervention Group (High Dose Fentanyl Sublingual Spray)

Received Fentanyl sublingual spray 10 minutes before performing second shuttle walk test, dose was 15-20% of morphine equivalent daily dose.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Sublingual Fentanyl for the Management of Breakthrough Pain	NCT02514252	Advanced Cancer...	Fentanyl Sublin... Questionnaires Mental Ability ... Study Diary	18 Years -	M.D. Anderson Cancer Center
Fentanyl Sublingual Spray in Treating Opioid-tolerant Cancer Patients With or Without Oral Mucositis	NCT00956254	Mucositis Pain Unspecified Adu...	Fentanyl sublin...	18 Years -	INSYS Therapeutics Inc
Fentanyl Sublingual Spray for Exercise-Induced Breakthrough Dyspnea	NCT02597478	Advanced Cancer...	Fentanyl Sublin... Shuttle Walk Te... Questionnaires Mental Ability ... Phone Call	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for fentanyl sublingual spray